This proposal requests support for a Keystone Symposia meeting entitled Lipid Biology and Lipotoxicity, organized by Scott A. Summers and Rudolf Zechner, which will be held in Killarney, Co. Kerry, Ireland from May 15 - 20, 2011. The accumulation of fat in tissues not suited for lipid storage has deleterious consequences on organ function, leading to cellular damage that underlies diabetes, heart disease, and hypertension. Illustrating the relationship is the fact that numerous effective therapeutics ameliorate metabolic disease symptoms by limiting the inappropriate deposition of fat in peripheral tissues (e.g., thiazolidinediones, metformin, or statins). Recent advances in genomics and lipidomics offer researchers an opportunity to make a substantial leap in the understanding and treatment of pathogenic conditions resulting from the excessive production and/or underutilization of fat. This meeting reviews these areas, placing specific emphasis on the following: (a) relationships between ectopic lipid deposition and metabolic disease;(b) mechanisms through which lipid excess alter tissue function;(c) regulatory processes that control lipid storage and metabolism;and (d) technological advances in the area of lipid analysis (i.e., lipidomics). Dedicated topics on cardiovascular disease will provide insight into the etiology of pathogenic events in the heart and numerous the sessions will advance knowledge on the fundamental relationships between abnormal fat metabolism and heart, lung, and blood disorders.